N-[3-(4-{3-[Bis(2-methylpropyl)amino]propyl}piperazin-1-yl)propyl]-1,2,3,4-tetrahydroacridin-9-amine which has the structure of Formula I:

belongs to a family of 1,4-bis(3-aminopropyl)piperazine derivatives previously disclosed in WO 2006/051489 and which are useful for the treatment and/or prevention of neurodegenerative diseases with APP dysfunction.
A majority of neurodegenerative diseases have common cellular and molecular mechanisms including protein aggregation and inclusion body formation.
The definition of the different types of lesions is made regarding the molecular compound which constitutes them. Neurofibrillary degeneration (NFD) is one of the most widely observed brain lesions which results from a cascade of molecular events combining abnormal modifications of the microtubule-associated Tau protein isoforms, their progressive aggregation and accumulation into fibrillar material inside neurons.
Tau protein is mainly expressed in neurons of the central nervous system where it interacts with tubulin to stabilize microtubules and promotes tubulin assembly into microtubules. This stabilizing property is controlled by isoforms and phosphorylation. The Tau isoforms are the product of alternative splicing from transcript of a single gene MAPT (microtubule-associated protein Tau) located on chromosome 17.
Six Tau isoforms exist in human brain tissue, and they are distinguished by their number of binding domains (three or four binding domains). The isoforms are a result of alternative splicing in exons 2, 3, and 10 of the Tau gene. The binding domains are located in the half carboxy-terminal region of the protein and are positively-charged (allowing it to bind to the negatively-charged microtubule). The isoforms with four binding domains containing exon 10 have a better affinity with microtubules, thus allowing a better stabilization of these microtubules, than those with three binding domains.
Tau is a phosphoprotein, the phosphorylation sites of which are essentially distributed on both sides of the microtubule binding domain. The phosphorylation of Tau results in disruption of microtubule organization.
In several neurodegenerative diseases termed “Tauopathies”, abnormally and hyperphosphorylated Tau protein isoforms aggregate into fibrillar structures within neurons to form the so-called neurofibrillary tangles (NFTs). These Tauopathies mainly differ from each other in both Tau isoform phosphorylation and content. Hyperphosphorylation, abnormal phosphorylation and aggregation are constantly present in neurofibrillary degeneration.
The quality, intensity and/or spatial location of neurofibrillary degeneration is extremely correlated with the impairment of cognitive functions. These impairments are particularly incapacitating for the patient who is not autonomous any more.
As a consequence, there is a need for treatments able to avoid the pathological aggregation of Tau protein in the human brain and the consequences of this aggregation.
Some treatments have focused on kinase inhibitors, phosphatase activators or anti-Tau antibodies (see for example WO 2014028777). However, none of these treatments have successfully led to a commercial treatment of Tauopathies up to the Applicant's knowledge, especially in the case of rare neurodegenerative diseases such as Pick's disease, Progressive supranuclear palsy (PSP), Corticobasal degeneration or Frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) mutations of MAPT.
There is thus still a need in the art for a treatment for Tauopathies able to successfully reestablish a normal Tau metabolism.